Glutamate and GABA concentrations following mild traumatic brain injury: a pilot study.

Animal models of mild traumatic brain injury (mTBI) suggest that metabolic changes in the brain occur immediately after a mechanical injury to the head. Proton magnetic resonance spectroscopy (1H-MRS) can be used to determine relative concentrations of metabolites in vivo in the human brain. The purpose of this study was to determine concentrations of glutamate and GABA in the brain acutely after mTBI and throughout 2 mo of recovery. Concentrations of glutamate and GABA were obtained using 1H-MRS in nine individuals who had suffered an mTBI and nine control individuals in two brain regions of interest: the primary motor cortex (M1), and the dorsolateral prefrontal cortex (DLPFC), and at three different time points postinjury: 72 h, 2 wk, and 2 mo postinjury. There were no differences between groups in concentrations of glutamate or GABA, or the ratio of glutamate to GABA, in M1. In the DLPFC, glutamate concentration was lower in the mTBI group compared with controls at 72 h postinjury (d = 1.02), and GABA concentration was lower in the mTBI group at 72 h and 2 wk postinjury (d = 0.81 and d = 1.21, respectively). The ratio of glutamate to GABA in the DLPFC was higher in the mTBI group at 2 wk postinjury (d = 1.63). These results suggest that changes in glutamate and GABA concentrations in the brain may be region-specific and may depend on the amount of time that has elapsed postinjury. NEW & NOTEWORTHY To our knowledge, this is the first study to examine neurotransmitter concentrations in vivo at multiple time points throughout recovery from mild traumatic brain injury in humans.

Sex, but not Apolipoprotein E Polymorphism, Differences in Spatial Performance in Young Adults.

The purpose of this study was to examine how sex and apolipoprotein E (APOE) genotype contribute to individual differences in spatial learning and memory. The associations of APOE genotype with neurocognitive function have been well studied among the elderly but less is known at earlier ages. Young adults (n = 169, 88 females) completed three neurocognitive tasks: mental rotation, spatial span, and Memory Island, a spatial navigation test. Males outperformed females on all three tasks: finding the hidden targets more quickly on Memory Island (Cohen's d = 0.62) and obtaining higher scores on mental rotation (d = 0.54) and spatial span (d = 0.37). In contrast, no significant effects of APOE were observed. The identified sex differences elaborate upon past literature documenting sexually dimorphic performance on specific neurobehavioral tasks.

Acute and longitudinal changes in motor cortex function following mild traumatic brain injury.

PRIMARY OBJECTIVE: To evaluate excitability and inhibition of the motor cortex acutely and longitudinally following mild traumatic brain injury (mTBI). RESEARCH DESIGN: A longitudinal paired case-control design was used to examine cortical excitability and inhibition in 15 adults who had sustained an mTBI (mean age = 20.8 ± 1.2 years) and 15 matched control participants (mean age = 21.1 ± 1.3 years). METHODS AND PROCEDURES: Participants visited the lab within 72 hours of injury and again at 1, 2, 4 and 8 weeks post-injury. During each visit, transcranial magnetic stimulation was used to examine resting motor threshold (RMT), motor evoked potential peak-to-peak amplitude (MEPamp) and cortical silent period (CSP) duration of the first dorsal interosseous muscle. MAIN OUTCOMES AND RESULTS: There were no differences between groups in RMT (p = 0.10) or MEPamp (p = 0.22) at 72 hours post-injury or across the 2-month testing period (p ≥ 0.68), indicating similar cortical excitability. However, the CSP duration was higher in individuals with mTBI, indicating greater intra-cortical inhibition compared with the control group at 72 hours post-injury (p = 0.03) and throughout the 2 months of recovery (p = 0.009). CONCLUSIONS: mTBI appeared to have little effect on cortical excitability, but an acute and long-lasting effect on intra-cortical inhibition.

Non-replication of an association of Apolipoprotein E2 with sinistrality.

A recent report found that left-handed adolescents were more than three times more likely to have an Apolipoprotein (APOE) ϵ2 allele. This study was unable to replicate this association in young adults (N=166). A meta-analysis of nine other datasets (N=360 to 7559, Power > 0.999) including that of National Alzheimer's Coordinating Center also failed to find an over-representation of ϵ2 among left-handers indicating that this earlier outcome was most likely a statistical artefact.

Motor Cortex Function in APOE4 Carriers and Noncarriers.

PURPOSE: The ε4 allele of the apolipoprotein-E gene has been associated with disease activity including Alzheimer disease, multiple sclerosis, and cardiovascular disease. Individuals who possess the ε4 variant of this gene (ε4 carriers) also demonstrate higher levels of cognitive impairment and lower motor scores compared with noncarriers. The purpose of this study was to establish whether there is a difference in motor cortex function between apoε4 carriers and noncarriers. We hypothesized that carriers would have lower levels of excitability and excitatory transmitter (glutamate) and similar levels of intracortical inhibition and inhibitory neurotransmitter (gamma-aminobutyric acid) than noncarriers. METHODS: Fifty-two participants provided saliva samples to determine apoε4 carrier status. Measures of motor cortex excitability and inhibition were obtained using transcranial magnetic stimulation, and measures of glutamate and gamma-aminobutyric acid concentrations were obtained using proton magnetic resonance spectroscopy. RESULTS: No significant differences in transcranial magnetic stimulation (P ≥ 0.19) or proton magnetic resonance spectroscopy measures (P ≥ 0.90) were found between carriers and noncarriers. CONCLUSIONS: The results from this study suggest that motor cortex function, as assessed by transcranial magnetic stimulation measures of excitability and inhibition, and MRS measures of excitatory and inhibitory neurotransmitter are similar in those who possess an apoε4 allele and those who do not.

Excitability, Inhibition, and Neurotransmitter Levels in the Motor Cortex of Symptomatic and Asymptomatic Individuals Following Mild Traumatic Brain Injury.

Purpose: The purpose of this study was to determine the level of excitability and inhibition, as well as the concentrations of excitatory and inhibitory neurotransmitters, in the motor cortex of individuals with acute and chronic symptoms from mTBI. Methods: Fifty-three individuals were assigned to one of four groups: (i) without history of mTBI (Control), (ii) within 72-h of diagnosis of mTBI (Acute), (iii) with history of mTBI and no remaining symptoms (Chronic Asymptomatic), and (iv) with chronic symptoms from mTBI, lasting at least 3 months post-injury (Chronic Symptomatic). Measures of corticospinal excitability and inhibition were obtained using transcranial magnetic stimulation (TMS). On the same day, measures of glutamate and GABA concentrations were obtained from the primary motor cortex (M1) using proton magnetic resonance spectroscopy. Results: MEP amplitude and area were both significantly lower in the Chronic Symptomatic group compared to the Control and Chronic Asymptomatic groups (p ≤ 0.05). Intracortical inhibition was not significantly different among groups (p = 0.14). The concentration of glutamate in M1 was similar between groups (p = 0.93) while there was a trend for a lower concentration of GABA in the Chronic Symptomatic group compared to the Acute group (p = 0.06). Conclusions: Individuals with chronic mTBI symptoms appear to have lower corticospinal excitability compared with acutely-injured individuals and asymptomatic controls, but the absence of differences in intracortical inhibition, and concentrations of excitatory and inhibitory neurotransmitters in M1 suggests that neurotransmitter changes in the human brain post-mTBI do not follow the pattern typically seen in the animal literature.

Reliability of glutamate and GABA quantification using proton magnetic resonance spectroscopy.

The consistency and reliability of proton magnetic resonance spectroscopy (1H-MRS) assessments of neurotransmitter concentration has not been widely examined over multiple days. The purpose of this study was to determine the reliability of glutamate and GABA measures using a single-voxel 1H-MRS protocol in healthy men and women. Glutamate and GABA quantitations were obtained from the primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) in 13 healthy individuals across 3 data collection sessions, including a baseline (Visit 1), 2-week (Visit 2), and 2-month time point (Visit 3). Glutamate concentrations were similar across visits in M1 (p=0.72) and the DLPFC (p=0.52). Reliability across days was excellent in M1 (R=0.93), and in the DLPFC (R=0.99). GABA concentrations were similar across visits in M1 (p=0.44) and in the DLPFC (p=0.59). Reliability of GABA concentration across days was excellent in M1 (R=0.93), and in the DLPFC (R=0.97). 1H-MRS is a reliable method for quantifying glutamate and GABA concentration in M1 and the DLPFC in humans.

Cortical and Physical Function after Mild Traumatic Brain Injury.

PURPOSE: The aim of this study was to prospectively examine the association between intracortical inhibition and functional recovery after mild traumatic brain injury (mTBI). METHODS: Twenty individuals with mTBI and 20 matched control participants were assessed using transcranial magnetic stimulation, the Attentional Network Test, and gait analysis. Hierarchical linear modeling was used to longitudinally examine potential differences between groups and relationships in the pattern of recovery in cortical silent period (CSP) duration, cognitive reaction time, and single- and dual-task walking speeds across five testing time points. Individuals with mTBI were assessed within 72 h of injury, and again at 1 wk, 2 wk, 1 month, and 2 months postinjury. After initial testing, control participants followed a similar timeline. RESULTS: At the 72-h time point, the group with mTBI had longer reaction time (b = -91.76, P = 0.01), similar single-task walking speed (b = 0.055, P = 0.10), and slower dual-task walking speed (b = 0.10, P = 0.012) compared with control participants. The CSP duration also tended to be longer in individuals with mTBI than controls at the 72-h time point (b = -16.34, P = 0.062). The change is CSP duration over time was not significantly associated with the change in reaction time (b = -0.19, P = 0.47), single-task walking speed (b = 0.0001, P = 0.53), or dual-task walking speed (b < 0.001, P = 0.68). CONCLUSION: Although cognitive and motor functions were significantly impaired in the mTBI group acutely after injury, levels of intracortical inhibition were not associated with recovery in either functional domain.

Motor Cortex Inhibition is Increased During a Secondary Cognitive Task.

The purpose of this study was to assess the effect of a cognitive task on motor cortex excitability and inhibition. Transcranial magnetic stimulation of the motor cortex was performed on 20 healthy individuals (18-24 years; 9 females) to measure motor evoked potentials (MEPs) and cortical silent periods at baseline, during, and following a secondary cognitive task. The MEP amplitude increased from 0.50 ± 0.09-0.87 ± 0.50 mV during a secondary cognitive task (p = .04), and returned to baseline (0.48 ± 0.31 mV; p = .90) posttask. The CSP duration also increased from 93.48 ± 28.76-113.6 ± 33.68 ms (p = .001) during the cognitive task, and returned to baseline posttask (89.0 ± 6.9 ms; p = .88). In the presence of a cognitive task, motor cortex excitability and inhibition were both increased relative to baseline. The increase in inhibition may help to explain the motor deficits experienced while performing a secondary cognitive task.